Wednesday, April 08, 2009

It all started back in May 2008, when JAMA (the Journal of the American Medical Association) published an article which reported the results of a clinical trial, funded by the National Institute for Mental Health, which showed that the anti-depressant drug Lexapro is effective in preventing depression among stroke patients.

The lead author of that study - Dr. Robert Robinson of the University of Iowa - disclosed being a consultant for two pharmaceutical companies, but he did not disclose any financial relationship with Forest Laboratories, the maker of Lexapro.

Clearly, a financial conflict of interest with Forest Laboratories would be most highly significant in relation to this research, because it tests the efficacy of Forest's Lexapro product. The absence of any disclosure related to Forest would lead readers to conclude that Dr. Robinson had no financial interest related to Forest Laboratories.

According to an article in MedPage Today, the next part of the story is as follows:

"The omission [of disclosure of a financial relationship with Forest Labs] was discovered by neuroanatomist Jonathan Leo, Ph.D., of Lincoln Memorial University in Harrogate, Tenn., and Jeffrey Lacasse, Ph.D., who teaches social work at Arizona State University. In October, they wrote to JAMA to point it out. They also decided to submit a lengthier analysis of the escitalopram [Lexapro] study and Dr. Robinson's apparent conflict of interest to BMJ. That analysis appeared in BMJ on March 5. Dr. Leo also passed along information on the conflict to a reporter at the New York Times. JAMA's editors eventually determined that Drs. Leo and Lacasse were correct, and in the March 11 issue, they published a correction and apology from Dr. Robinson."

Dr. Robinson's published correction acknowledged that Leo and Lacasse were correct, and that he had received honoraria from Forest Labs for speaking engagements: "In October 2004, he received honoraria and expenses for 2 presentations in Tucson, Arizona, which were sponsored by Forest Laboratories and paid through the intermediary, Sudler and Hennessey, New York, New York. He was a member of the speakers' bureau for Forest Laboratories in 2004 and perhaps 2005."

In its March 20, 2009 issue, JAMA published an editorial in which it criticized Dr. Leo for having gone public with his assertion that Dr. Robinson had a conflict of interest with Forest Labs that was not disclosed in the article, and for having published a letter in BMJ making such an assertion. The Journal also acknowledged trying to have Leo reprimanded by his superiors for his behavior:

"While the confidential investigation of unreported conflicts of interest is under way, we consider involvement of third parties— such as Leo had done by his posting on the BMJ site and by contacting the media—to be a serious ethical breach of confidentiality that not only potentially damages our ability to complete a fair and thorough investigation (of the specific issue that Leo had brought to our attention), but also potentially damages JAMA’s reputation by the insinuation that we would fail to do so. A telephone conversation intended to inform Leo that his actions were inappropriate transformed into an argumentative discussion, as Leo continued to refuse to acknowledge any problems with his actions, even after he was informed that the investigation was completed and was advised to read the upcoming March 11 issue of JAMA (where the letter of explanation and apology from Robinson and the formal correction were in press). Leo also was informed that, if his actions represented his apparent lack of confidence in and regard for JAMA, he certainly should not plan to submit future manuscripts or letters for publication."

"Although we appreciated Leo alerting us to the potential omission of some financial disclosure information by Robinson, we maintain that his actions were inappropriate in contacting the media and by his posting on the BMJ Web site prior to publication of the correction and letter ofapology from Robinson. However, since Leo apparently did not appreciate the serious implications of his actions, despite our attempts to explain, we felt an obligation to notify the dean of his institution about our concerns of how Leo’s actions were potentially damaging to JAMA’s reputation." ...

"As a result of these recent events we are making the following modifications to our already rigorous approach for investigations into allegations of unreported potential conflicts of interest. JAMA will require that the individual bringing the allegations ... should not reveal this information to third parties or the media while the investigation is under way...".

The story actually gets a little juicier. The author of the Wall Street Journal health blog asserts that when he spoke to JAMA's editor to question her about the issue, she said of Dr. Leo: "This guy is a nobody and a nothing. He is trying to make a name for himself. Please call me about something important." In the March 20 editorial, the JAMA editor denies this assertion.

In another interesting assertion, the Wall Street Journal health blog writer states that when Dr. Leo was called by an associate editor at JAMA, that editor told him: "Who do you think you are? You are banned from JAMA for life. You will be sorry. Your school will be sorry. Your students will be sorry." In the March 20 editorial, JAMA's editors also deny this assertion.

What is clear, however, is that JAMA did speak to Dr. Leo's superiors and attempted to have him reprimanded in some way, as the editors acknowledge this in their editorial.

The Rest of the Story

I think JAMA's new policy is off-base. I find it inappropriate for JAMA to try to dictate the behavior of parties with which it has not entered into a contractual relationship of any sort. Thus, I believe the policy is unduly restricting the free speech rights of third parties who have no relationship of any sort with the journal.

If someone wants to write a criticism of an article that is published in JAMA, does that individual need to hold off on criticizing the article until JAMA conducts an internal investigation to see if that criticism is warranted? Of course not. Such a policy would be ludicrous and would be viewed as a completely unwarranted intrusion into free speech.

If someone wanted to criticize an article based on the grant funding of the authors, would the journal have a legitimate interest in controlling the conditions under which the individual publishes or expresses his criticism? Of course not.

So if an individual has documented information that an author of an article has a relevant and significant conflict of interest, then why is it not permissible for that individual to express her opinion?

While it is perfectly acceptable for a journal to restrict the speech of individuals with whom it has entered into a contractual relationship (such as study authors), the journal cannot legitimately expect to regulate the behavior of third parties with which it has no relationship.

For example, if a researcher submits a paper to a journal, that journal has a legitimate interest in making sure that the results of the study are not released to the media prior to publication. Thus, is it perfectly appropriate for journals to establish a policy that authors may not contact the media about a study until it appears in print. This is, in fact, a common policy of many journals. It is appropriate because by submitting an article to a journal, the author has entered into a contractual relationship with the journal, and thus the journal has standing to require the author to follow certain policies, including withholding information from the media prior to publication.

However, an individual who is critical of an article for failure to disclose a conflict of interest and a concern for how that conflict may have affected the study results and conclusions is not a party to any contractual relationship with the journal. How can the journal expect to be able to dictate the behavior of that individual, especially in terms of infringing upon that individual's free speech rights.

I would argue that it is not only appropriate for individuals to be willing to publicly share critiques of published articles (including critiques that are based on conflicts of interest of study authors), but it is also critical to the integrity of science and scientific knowledge.

What JAMA is doing is basically stifling potential criticism of research based on undisclosed conflicts of interest. Researchers may be reluctant to report a conflict of interest or to express any criticism related to conflict of interest because of fear of retaliation by the journal. This is especially true in light of the extraordinary action taken by the journal to try to have Dr. Leo reprimanded.

But the bottom line is that Dr. Leo did nothing wrong. There was no misconduct whatsoever. He expressed legitimate criticism of the article. The journal, in fact, acknowledged that his criticism was correct and Dr. Robinson corrected the flawed disclosure.

The only wrongdoing would have been if Dr. Leo was wrong in his assertion that Dr. Robinson had an undisclosed conflict of interest. If someone is going to publicly assert that a conflict of interest exists, then it is imperative that the individual have clear documentation of that conflict. But if the individual has the documentation, then it is his or her legitimate right to speak out and express an opinion about the research and the journal has no place reprimanding or trying to punish the individual for expressing his or her opinion.

The Association of Health Care Journalists has responded to this story with similar sentiments: "JAMA's editorial says the researcher's actions constituted 'a serious ethical breach of confidentiality that not only potentially damages our ability to complete a fair and thorough investigation ... but also potentially damages JAMA's reputation by the insinuation that we would fail to (investigate).' To the contrary, science requires a full and open hearing of information. Allowing scrutiny of possible conflicts of interest by the public and the media ultimately leads to greater transparency and trust. JAMA would better serve the public by focusing its efforts on diligently identifying researchers who fail to report conflicts of interest rather than intimidating those who seek to ensure that the public is fully informed."

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About Me

Dr. Siegel is a Professor in the Department of Community Health Sciences, Boston University School of Public Health. He has 32 years of experience in the field of tobacco control. He previously spent two years working at the Office on Smoking and Health at CDC, where he conducted research on secondhand smoke and cigarette advertising. He has published nearly 70 papers related to tobacco. He testified in the landmark Engle lawsuit against the tobacco companies, which resulted in an unprecedented $145 billion verdict against the industry. He teaches social and behavioral sciences, mass communication and public health, and public health advocacy in the Masters of Public Health program.